The major objective of this research continues to be elucidation of basic mechanisms of energy control, with emphasis being placed upon potential differences between cancer and normal cells. The hope is to eventually explain the molecular basis for unique aspects of cancer metabolism and thereby open additional avenues of therapy. The effort of the past years has focused on the pyruvate kinase isozymes. Three basic isozymes have been isolated and studied. It also is known that here is a switching from one to another of these isozymes during normal development and switching back during neoplastic development. Thus it appears that there is a particular molecular form of pyruvate kinase associated with fetal or cancerous tissues. Elucidation of the mechanism by which a tissue switches from one to another isozyme would provide an understanding of control at the genetic or translational level. Loss of this control presumably accompanies the transition of a normal cell to a cancerous one. Moreover, the association of a particular isozyme of pyruvate kinase with rapidly growing cells, may relate to the high anaerobic glycolytic capacity of such cells. The first phase of investigation into these basic phenomena will be to continue studies of the structural-functional relationships of the pyruvate kinase isozymes. The philosophy being that the nature and consequences of the change in the products need be understood. These studies also will relate structure to function. The second phase of the proposed studies will involve investigation of the presumed phenomena of enzyme induction and repression.